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Composite B-cell and T-cell lymphomas:clinical,pathological,and molecular features of three cases and literature review

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第8期24卷 711-722页

作者： Xueli JIN Hui LIU Jing LI Xibin XIAO Xianggui YUAN Panpan CHEN Boxiao CHEN Yun LIANG fengbo huang Department of Hematology the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China Department of Pathology the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China Department of Nuclear Medicine the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China School of Medicine Zhejiang UniversityHangzhou 310029China

Composite lymphoma(CL)involving B-cell lymphoma and T-cell lymphoma is extremely rare.Herein,we report three such cases using immunohistochemistry,flow cytometry,and the next-generation sequencing(NGS)to identify the pathological and molecular characteristics of CL.In the first case,the patient was admitted to hospital for generalized pruritic maculopapular rash over the whole body.An excisional biopsy of the skin lesions showed T-cell lymphoma.At the same time,the staging bone marrow(BM)biopsy revealed a diffuse large B-cell lymphoma(DLBCL).After R-CHOP(rituximab,cyclophosphamide,doxorubicin,vincristine,and prednisone)therapies,the patient produced a good response with substantial dissipation of the rashes and relief of skin.The other two patients were admitted to hospital due to lymphadenopathy and were diagnosed with DLBCL and follicular lymphoma(FL)after core needle biopsy of lymph nodes,BM biopsy,BM aspiration,and flow cytometry.Following R-CHOP and R-COP(rituximab,cyclophosphamide,vincristine,and prednisone)therapies,they achieved complete remission unconfirmed(CRu)and complete remission(CR).However,one or two years later,they suffered a relapse of lymphadenopathy.The shocking fact was that re-biopsy of lymphadenopathy revealed peripheral T-cell lymphoma(PTCL)and angioimmunoblastic T-cell lymphoma(AITL).NGS findings identified DNA methyltransferase 3a(DNMT3a),isocitrate dehydrogenase 2(IDH2),Ras homolog gene family,member A(RHOA),splicing factor 3B subunit 1(SF3B1),and tumor protein p53(TP53)mutations.After immunochemotherapy,these patients achieved CRu and CR again.Nevertheless,they suffered a second relapse of T-cell lymphoma.Finally,they died due to progression of disease.We found that the occurrence of CL is associated with Epstein-Barr virus infection and DNMT3a,IDH2,and TP53 mutations,and the prognosis of the disease is closely related to the T-cell lymphoma components.

关键词： Composite lymphoma B-cell lymphoma T-cell lymphoma

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Expanding the horizons of targeted protein degradation:A non-small molecule perspective

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2402-2427页

作者： Xiaowei huang fengbo Wu Jing Ye Lian Wang Xiaoyun Wang Xiang Li Gu He Department of Pharmacy and Department of Dermatology&Venerology West China HospitalSichuan UniversityChengdu 610041China Department of Urology West China HospitalSichuan UniversityChengdu 610041China Laboratory of Dermatology Clinical Institute of Inflammation and ImmunologyFrontiers Science Center for Disease-Related Molecular Network and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Targeted protein degradation(TPD)represented by proteolysis targeting chimeras(PROTACs)marks a significant stride in drug discovery.A plethora of innovative technologies inspired by PROTAC have not only revolutionized the landscape of TPD but have the potential to unlock functionalities beyond degradation.Non-small-molecule-based approaches play an irreplaceable role in this field.A wide variety of agents spanning a broad chemical spectrum,including peptides,nucleic acids,antibodies,and even vaccines,which not only prove instrumental in overcoming the constraints of conventional small molecule entities but also provided rapidly renewing paradigms.Herein we summarize the burgeoning non-small molecule technological platforms inspired by PROTACs,including three major trajectories,to provide insights for the design strategies based on novel paradigms.

关键词： Targeted protein degradation Proteolysis targeting chimera Endocytosis Autophagy Proximity-inducing modality Post-translational modification

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Fatigue Crack Initiation and Propagation Dominated by Crystallographic Factors in TiB/near a-Ti

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Acta Metallurgica Sinica(English Letters) 2024年第5期37卷 763-776页

作者： Fanchao Meng Rui Zhang Shuai Wang fengbo Sun Run Chen Lujun huang Lin Geng School of Materials Science and Engineering Harbin Institute of TechnologyHarbin 150001China Waikato Centre for Advanced Materials and Manufacturing School of EngineeringUniversity of WaikatoHamilton 3240New Zealand State Key Laboratory of Advanced Welding and Joining Harbin Institute of TechnologyHarbin 150001China

Discontinuously reinforced titanium matrix composites(DRTMCs)with a network structure have been extensively researched due to their superior combination of strength and ductility.However,their fatigue performance has remained unknown.In order to elucidate the fatigue behavior of DRTMCs,a tension-tension fatigue test was performed on a TiB/nearα-Ti composite with network structure.The results showed that the variability of fatigue lifetime increased as the stress level decreased.Fractography analysis indicated that fatigue crack initiation was associated with facet formation,while the subsequent propagation was hindered by the network structure comprising TiB whiskers and silicides.Crystallographic characterization further revealed that facets formed due to a combination of shear and normal stress.The reduction in fatigue lifetime was attributed to an increase in the effective slip length,which was influenced by the orientation of grains near the crack-initiation sites toward basal slip in the life-limiting specimen.Quasi in situ observation suggested that the crack initiation was facilitated by both basal and prismatic slip ofα-Ti as well as fracture of TiBw.Crack propagation was found to be associated with basal and prismatic slip systems with high Schmid factors,regardless of whether the crack was intergranular or intragranular.

关键词： Titanium matrix composite TiBw Fatigue lifetime variability Crack initiation Crack propagation

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Hot deformation behavior and microstructure evolution of GH3536-TiB2 composites fabricated by powder metallurgy

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Science China Technological Sciences 2024年第7期67卷 2107-2124页

作者： ZHOU ShiPeng WANG Shuai huang LuJun ZHANG Rui CHEN Xin MENG FanChao CHEN Run SUN fengbo WANG CunYu GENG Lin School of Materials Science and Engineering Harbin Institute of Technology State Key Laboratory of Advanced Welding and Joining Harbin Institute of Technology Waikato Centre for Advanced Materials and Manufacturing School of Engineering University of Waikato

The hot deformation behavior and microstructure evolution of GH3536-TiB2composites fabricated by powder metallurgy（PM）were examined in the temperature range of 950–1150°C and strain rate range of 0.001–1 s-1. The hot compression stress-strain curves and the constitutive equation were obtained. In addition, the hot processing map was drawn, which indicated that the appropriate hot working window was 950–1050°C/0.001–0.1 s-1and 1050–1100°C/0.001–0.01 s-1. The microstructure analysis showed that the splitting and spheroidization of M3B2led to a decrease in size and volume fraction at 950–1100°C. At 1150°C,the eutectic microstructure of M3B2+ γ was formed due to the dissolution of M3B2, which caused macroscopic cracking of the deformed sample. Additionally, the deformation temperature and the strain rate had little effect on the size and volume fraction of M3B2. Besides, discontinuous dynamic recrystallization（DDRX） and continuous dynamic recrystallization（CDRX） were found in the deformed microstructure, while the former was dominant. Within the test range of this work, the dynamic recrystallization（DRX） fraction of the deformed composites was high due to the bulging nucleation of numerous interfaces. The DRX grain size increased with increasing deformation temperature or decreasing strain rate. Texture analysis showed that the deformation texture of //compression direction RD existed in the matrix when the deformation temperature was below 1100°C, and the texture type became //RD at 1100°C. Additionally, it was also found that the //RD texture was formed in M3B2under the strain rates of 0.1 and 0.01 s-1.

关键词： GH3536 alloy matrix composites powder metallurgy hot deformation behavior microstructure evolution

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Hot deformation behavior and microstructure evolution of GH3536-TiBcomposites fabricated by powder metallurgy

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Science China Technological Sciences 2024年

The hot deformation behavior and microstructure evolution of GH3536-TiB2composites fabricated by powder metallurgy(PM)were examined in the temperature range of 950–1150°C and strain rate range of 0.001–1s-1. The hot compression stress-strain curves and the constitutive equation were obtained. In addition, the hot processing map was drawn, which indicated that the appropriate hot working window was 950–1050°C/0.001–0.1 s-1and 1050–1100°C/0.001–0.01 s-1. The microstructure analysis showed that the splitting and spheroidization of M3B2led to a decrease in size and volume fraction at 950–1100°C. At 1150°C,the eutectic microstructure of M3B2+ γ was formed due to the dissolution of M3B2, which caused macroscopic cracking of the deformed sample. Additionally, the deformation temperature and the strain rate had little effect on the size and volume fraction of M3B2. Besides, discontinuous dynamic recrystallization(DDRX) and continuous dynamic recrystallization(CDRX) were found in the deformed microstructure, while the former was dominant. Within the test range of this work, the dynamic recrystallization(DRX) fraction of the deformed composites was high due to the bulging nucleation of numerous interfaces. The DRX grain size increased with increasing deformation temperature or decreasing strain rate. Texture analysis showed that the deformation texture of //compression direction RD existed in the matrix when the deformation temperature was below 1100°C, and the texture type became //RD at 1100°C. Additionally, it was also found that the //RD texture was formed in M3B2under the strain rates of 0.1 and 0.01 s-1.

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涎腺微分泌性腺癌1例

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中华病理学杂志 2022年第3期51卷 256-258页

作者：贺晓娟黄封博相学平李金范浙江大学医学院附属第二医院病理科杭州310009

微分泌性腺癌(MSA)是一种新近命名的涎腺肿瘤,具有显著一致的临床、组织学、免疫表型和特征性MEF2C-SS18基因融合的遗传学特征。本例患者男性,27岁,发现右颊肿物4个月。镜下表现,免疫组织化学染色及SS18分离荧光原位杂交检测结果符合MS... 详细信息

微分泌性腺癌(MSA)是一种新近命名的涎腺肿瘤,具有显著一致的临床、组织学、免疫表型和特征性MEF2C-SS18基因融合的遗传学特征。本例患者男性,27岁,发现右颊肿物4个月。镜下表现,免疫组织化学染色及SS18分离荧光原位杂交检测结果符合MSA诊断。MSA是一种独特的、低级别唾液腺癌。

关键词：分泌性荧光原位杂交免疫表型涎腺肿瘤基因融合免疫组织化学染色遗传学特征 MSA

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Associations of daily sedentary behavior,physical activity,and sleep with irritable bowel syndrome:A prospective analysis of 362,193 participants

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Journal of Sport and Health Science 2024年第1期13卷 72-80页

作者： Xu Gao Sifan Tian Ninghao huang Gang Sun Tao huang Department of Occupational and Environmental Health Sciences School of Public HealthPeking UniversityBeijing 100191China Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijing 100191China Department of Gastroenterology and Hepatology First Medical Center of People's Liberation Army General HospitalBeijing 100853China

Background:Irritable bowel syndrome(IBS)substantially affects quality of life and requires early prevention.This study aimed to elucidate the relationships between IBS and daily behaviors,including sedentary behavior(SB),physical activity(PA),and sleep.In particular,it seeks to identify healthy behaviors to reduce IBS risk,which previous studies have rarely addressed.Methods:Daily behaviors were retrieved from self-reported data of 362,193 eligible UK Biobank participants.Incident cases were determined by self-report or health care data according to RomeⅣcriteria.Results:A total of 345,388 participants were IBS-free at baseline,during a median follow-up of 8.45 years,19,885 incident IBS cases were recorded.When examined individually,SB and shorter(≤7 h/day)or longer(>7 h/day)sleep duration were each positively associated with increased IBS risk,and PA was associated with lower IBS risk.The isotemporal substitution model suggested that replacing SB with other activities could provide further protective effects against IBS risk.Among people sleeping≤7 h/day,replacing 1 h of SB with equivalent light PA,vigorous PA,or sleep was associated with 8.1%(95%confidence interval(95%CI):0.901-0.937),5.8%(95%CI:0.896-0.991),and 9.2%(95%CI:0.885-0.932)reduced IBS risk,respectively.For people sleeping>7 h/day,light and vigorous PA were associated with a 4.8%(95%CI:0.926-0.978)and a 12.0%(95%CI:0.815-0.949)lower IBS risk,respectively.These benefits were mostly independent of genetic risk for IBS.Conclusion:SB and unhealthy sleep duration are risk factors for IBS.A promising way to mitigate IBS risk for individuals sleeping≤7 h/day and for those sleeping>7 h/day appears to be by replacing SB with adequate sleep or vigorous PA,respectively,regardless of the genetic predisposition of IBS.

关键词： Irritable bowel syndrome Isotemporal substitution model Physical activity Sedentary behavior Sleep

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Fast Blood Oxygenation through Hemocompatible Asymmetric Polymer of Intrinsic Microporosity Membranes

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Research 2024年第1期2023卷 261-270页

作者： Xinxi huang Junping huang Pengcheng Su Wanbin Li Guangdong Key Laboratory of Environmental Pollution and Health School of EnvironmentJinan UniversityGuangzhou 511443China

Membrane technology has attracted considerable attention for chemical and medical applications,among others.Artificial organs play important roles in medical science.A membrane oxygenator,also known as artificial lung,can replenish O_(2) and remove CO_(2) of blood to maintain the metabolism of patients with cardiopulmonary failure.However,the membrane,a key component,is subjected to inferior gas transport property,leakage propensity,and insufficient hemocompatibility.In this study,we report efficient blood oxygenation by using an asymmetric nanoporous membrane that is fabricated using the classic nonsolvent-induced phase separation method for polymer of intrinsic microporosity-1.The intrinsic superhydrophobic nanopores and asymmetric configuration endow the membrane with water impermeability and gas ultrapermeability,up to 3,500 and 1,100 gas permeation units for CO_(2) and O_(2),respectively.Moreover,the rational hydrophobic–hydrophilic nature,electronegativity,and smoothness of the surface enable the substantially restricted protein adsorption,platelet adhesion and activation,hemolysis,and thrombosis for the membrane.Importantly,during blood oxygenation,the asymmetric nanoporous membrane shows no thrombus formation and plasma leakage and exhibits fast O_(2) and CO_(2) transport processes with exchange rates of 20 to 60 and 100 to 350 ml m^(−2) min^(−1),respectively,which are 2 to 6 times higher than those of conventional membranes.The concepts reported here offer an alternative route to fabricate high-performance membranes and expand the possibilities of nanoporous materials for membrane-based artificial organs.

关键词： porosity asymmetric Oxygen

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A thermodynamic perspective on electrode poisoning in solid oxide fuel cells

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International Journal of Minerals,Metallurgy and Materials 2024年第6期31卷 1449-1455页

作者： Kevin huang Department of Mechanical Engineering University of South CarolinaColumbiaUSA

A critical challenge to the commercialization of clean and high-efficiency solid oxide fuel cell(SOFC)technology is the insuf-ficient stack lifespan caused by a variety of degradation mechanisms,which are associated with cell components and chemical feedstocks.Cell components related degradation refers to thermal/chemical/electrochemical deterioration of cell materials under operating conditions,whereas the latter regards impurities in feedstocks of oxidant(air)and reductant(fuel).This article provides a thermodynamic perspective on the understanding of the impurities-induced degradation mechanisms in SOFCs.The discussion focuses on using thermodynamic ana-lysis to elucidate poisoning mechanisms in cathodes by impurity species such as Cr,CO_(2),H_(2)O,and SO_(2) and in the anode by species such as S(or H_(2)S),SiO_(2),and P_(2)(or PH_(3)).The author hopes the presented fundamental insights can provide a theoretical foundation for search-ing for better technical solutions to address the critical degradation challenges.

关键词： impurities air fuel reaction activity

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In situ direct reprogramming of astrocytes to neurons via polypyrimidine tract-binding protein 1 knockdown in a mouse model of ischemic stroke

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Neural Regeneration Research 2024年第10期19卷 2240-2248页

作者： Meng Yuan Yao Tang Tianwen huang Lining Ke En huang Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Human Anatomy School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina Scientific Research Center School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology Fujian Medical University Union HospitalFuzhouFujian ProvinceChina Fujian Key Laboratory of Vascular Aging Fujian Medical UniversityFuzhouFujian ProvinceChina

In situ direct reprogramming technology can directly convert endogenous glial cells into functional neurons in vivo for central nervous system repair. Polypyrimidine tract-binding protein 1(PTB) knockdown has been shown to reprogram astrocytes to functional neurons in situ. In this study, we used AAV-PHP.e B-GFAP-sh PTB to knockdown PTB in a mouse model of ischemic stroke induced by endothelin-1, and investigated the effects of GFAP-sh PTB-mediated direct reprogramming to neurons. Our results showed that in the mouse model of ischemic stroke, PTB knockdown effectively reprogrammed GFAP-positive cells to neurons in ischemic foci, restored neural tissue structure, reduced inflammatory response, and improved behavioral function. These findings validate the effectiveness of in situ transdifferentiation of astrocytes, and suggest that the approach may be a promising strategy for stroke treatment.

关键词： astrocyte in situ direct reprogramming ischemic stroke miR-30 based shRNA neuron polypyrimidine tract-binding protein 1 transdifferentiation

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